Certain aminoalkylamino substituted azacycloalkenes



United States Patent 3,518,251 CERTAIN AMINOALKYLAMINO SUBSTITUTED AZACYCLOALKENES Karl Gatzi, Basel, Switzerland, assignor to J. R.- Geigy, Basel, Switzerland No Drawing. Continuation-impart of application Ser. No.

290,343, June 25, 1963. This application June 7, 1967,

Ser. No. 644,078

Int. Cl. C07d 27/14, 29/38, 41/08 US. Cl. 260-239 8 Claims ABSTRACT OF THE DISCLOSURE Fungicidal heterocyclic amines of the formula C-NH-(CH2)yNH-RI nHZn I wherein n is a whole number from 3 to 15,

y is a ,whole number from 2 to 6, and

R represents hydrogen or alkyl, cycloalkyl, aryl or aralkyl radicals or heterocyclic radicals,

as well as fungicidally effective salts of such amines with organicor inorganic acids, and their quaternary salts, and fungicidal compositions containing such novel compounds.

CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation-in-part of our pending application Ser. No. 290,343, filed June 25, 1963, now US. Pat; 3,378,438, granted Apr. 16, 1968, which 'is in turn a continuation-in-part of our patent application -Ser. No. 290,308, filed on June 25, 1963, now Pat. No. 3,255,181, granted June 7, 1966.

.' DESCRIPTION OF THE INVENTION This invention relates to certain heterocyclic amines possessing fungicidal activity, or compositions containing these amines as active ingredients, which are useful in controlling the growth of fungi by application of such compounds or compositions to the fungi or the substrate --on which they grow.

I It has been found that certain falling under the formula heterocyclic amines wherein R represents hydrogen, an alkyl, cycloalkyl, aryl or aralkyl radical which is unsubstituted or substituted, or a heterocyclic radical, all radicals being defined more specifically below,

and wherein:

y represents a whole number of 2 to 6, and n represents a whole number from 3 to 15,

3,518,251 Patented June 30, 1970 wherein R represents a lower alkyl radical having 1 to 3 carbon atoms,

Q represents oxygen or sulfur, and

n has the above given meaning, preferably in the presence of an organic solvent and of a tertiary amine as catalyst, with a primary amine of the formula wherein y and R have the meanings given above. As organic solvents, e.g. aromatic hydrocarbons, alcohols, esters, ketones, ethers, etc. are used.

Examples of tertiary amines are pyridine, trimethylamine, triethylamine, triethanolamine, etc. In the reaction, the radical QR is split olf and an alcohol or mercaptan is formed.

By the term salts are meant salts of inorganic and organic acids as well as the quaternary salts. The salts of inorganic and organic acids with compounds of Formula I are obtained by reacting, optionally in the presence of neutral organic solvents or of water, the reaction products obtained by the process described with equivalent amounts of an inorganic or organic acid such as hydrochloric acid, sulfuric acid, phosphoric acid, formic acid, acetic acid, propionic acid, sorbic acid, oxalic acid, succinic acid, phthalic acid, p-toluene sulfonic acid, lauryl sulfuric acid, lauric acid, and others.

The quaternary salts are obtained by reacting equivalent amounts of compounds of Formula I with conventional quaternising agents, e.g. reactive esters of sulfuric acid and toluene sulfonic acid, or reactive derivatives of alcohols, e.g. methyl iodide, butyl bromide or benzyl chloride. This reaction may be performed in the presence of an organic inert solvent e.g. benzene, or of Water.

By the symbol C,,H in the Formulas I and II are meant alkylene radicals with from 3 to 15 carbon atoms which may be substituted by branched or straight chain alkyl radicals, but of which from 3 to not more than 7 carbon atoms are ring members of ring A.

More specifically, R in Formula I represents hydrogen, alkyl with from 1 to 15 carbon atoms, alkoxy-alkyl with from 3 to 15 carbon atoms, alkylthio'alkyl with from 3 to 15 carbon atoms, chloroalkyl with from 2 to 15 carbon atoms, bromo-alkyl with from 2 to 15 carbon atoms, phenyl, lower alkyl-phenyl, lower alkoxy-phenyl, chloro-phenyl, bromo-phenyl, phenyl-lower alkyl, lower cycloalkyl with from 5 to 7 carbon atoms, and lower alkyl, chloro-phenyl-lower alkyl, bromophenyl-lower alkyl, cycloalkyl with from 5 to 7 carbon atoms, and lower alkylcycloalkyl with from 5 to 7 ring carbon atoms; and, furthermore A -azacyclopentenyl-(5 lower alkyl-A azacyclopentenyl-(S), A -azacycloheptenyl-(7), lower alkyl-A -azacycloheptenyl-(7 A -azacyc1ononenyl-( 9) and lower alkyl-A -azacyclononenyl-(9 Lower when used in connection with alkyl or alkoXy means a radical with from 1 to 4 carbon atoms.

The following examples describe the production of the active substances according to the invention. Parts are given therein as parts by weight unless stated otherwise and the temperatures are in degrees centigrade.

EXAMPLE 1 12.7 parts of O-methyl caprolactim 17.2 parts of fl-(n-octylamino)-ethylarnine, 200 parts by volume of ethanol and 1.0 part of triethylamine are refluxed for 20 hours. The main amount of the ethanol is then evaporated off in vacuo and the residue is taken up in ether and O-me thyl caprolactim produced as described in Organic Synthesis, 31, 72 (1951).

B-(n-Oetyl'amino)-ethylamine produced as described by F. Linsker et al., J. Amer. Chem. $00., 67 (1945), 1581.

EXAMPLE 2 On dissolving in the equivalent amount of dilute hydrochloric acid, the hydrochloride is obtained (recrystallized from water or acetone).

EXAMPLE 3 In an analogous manner, there are produced from 7-[ 8-(n-octylamino) ethylamino] 3,4,5,6 1 tetrahydro- 2H-azepine and the corresponding dilute acid the sulfate, nitrate, phosphate, formate, acetate, propionate, sorbate, oxalate, succinate, fumerate, phthalate, p-toluenesulfonate, benzoate, lauryl sulfate and laurate.

EXAMPLES 4 AND 5 14.3 parts of Z-methylthio 3,4,5,6 tetrahydro-ZH- azepine, 200 parts by volume of benzene, 15.0 parts of 'y-phenylamino propylamine and 1 part of triethylamine are refluxed for 20 hours. The solution is concentrated in vacuo and the residue is recrystallized from petroleum ether; the 7-( -phenylamino propylamino) 3,4,5,6- tetrahydro-ZH-azepine is then converted to the hydrochloride according to Example 1.

EXAMPLE 6 7 parts of 7-(y-phenylamino propylamino) 3,4,5,6- tetrahydro-ZH-azepine are dissolved in 100 parts by volume of anhydrous benzene, and 3.25 parts of dimethylsulfate are added drop by drop and the resulting mixture is then refluxed for one hour. On evaporating the benzene the quaternary 7-(7-phenylamino propylamino)-3,4,5, 6 tetrahydro-ZH-azepine dimethylsulfate is obtained as water-soluble, viscous oil which decomposes upon distillation.

Further compounds of Formula I of which the data for n, z which represents the number of carbon atoms being ring members in ring A besides the --C=N grouping, the alkyl branching at ring A, if present, y, as well as R are given in the table below, and salts and quaternary salts of these compounds of which the anion or quaternizing agent is also given below, are produced in the manner described in Examples 1 to 6 from equivalent amounts of the corresponding lactim ether of Formula II and the corresponding amine of Formula III.

The starting materials are either known or have been produced in a manner analogous to that of making the known starting materials.

' 4 EXAMPLES 34 AND 35 The two following compounds are obtained in "the same manner as described, in Examples 1 and 2 from enanth lactam and capryl lactam by reaction with fl-(n- 0ctylamino)-ethylamine and -phenylamino-propylaminerespectively.

The compounds of the Formula I are suitable as active substances in fungicidal agents for the most variousforms of application such as inhibition and repression of the growthof fungi on plants and parts thereof as well as the protection of organic materials of all types such as wood, textiles, furs, leather, paper, synthetic substances, etc. from attack and decomposition by fungi. For these'purposes the active substances are employed in a finely distributed form as such or combined with suitable carriers and distributing agents. They can also be used in combination with other fungicidally active substances as well as with fungistatica and bacteriostatica. "To increase the range of action, also insecticidally or nematocidally active substances, etc. can be added to the active substances use according to the invention. 7

To produce fungicidal agents according to the invention the active substances can be mixed, for example, with solid, pulverulent carriers such as, e.g. talcum, kaolin, loess, chalk or ground limestone. If desired, the pulverulent agents obtained can be made suspendable in water by the addition of suitable wetting and dispersing agents such as sulphite waste liquor. In addition, the a'ctive'substances as such in solid, finely ground form, can be suspended in water with the aid of capillary active substances, or they can be emulsified in water, after dissolving them in organic solvents, with the aid of suitable emulsifying agents. Also, the active substances can be dissolved in organic solvents, e.g. in chlorinatedhydrocarbons such as trichloroethylene, or in medium petrol- Al kyl z branching y R1 Salt Hydrogen p-Chloro-pheny n-Hexyl A -azacycloheptenyl-(7) o-Clalorophenyl 5 Larnyl 7 B-(n-hexyloxy) -ethyl 4-t-butyl-A -alzacyeloheptenyl-(n B-(p-methy1-phenyll-cthyl: I

8-ethy1-A -azacyclononenyl-(9 2 o-Methyl-benzyl A -azacyclopentenyl-(5) leurn fractions, boiling range 100 to 200 possibly with the addition of auxiliary solvents such as acetone or higher ketones, e.g. cyclohexanone. Finally, the active substances can also be employed in the form of aerosols, smoke or mist, particularly in storerooms and greenhouses.

The fungicidal active substances are applied to an organic material to be protected generally either by adin the table represents at least a 90% inhibition of germination attained by the residue of one ml. of the aforesaid 1% solution of active substance in acetone (:13 meg. active substance per cm. represents the same effect attained by the residue of one ml. of the aforesaid 0.1% solution, and the same effect attained with the residue of one ml. of 0.01% solution of active substance.

Alt. B tr. Clast. Con]. Fus. Muc. Pen. Stem. ten. cm. 0. dipl. culm. spec. spec. cons.

"---tli-th1llht E 1 1.{taaat;at.gmrea rslrmrsraaaamass;

heritene mixture therewith, by spraying or by impregnating with I claim: organic-aqueous or aqueous solutions of the active sub- 1. A compound selected from stance which can contain the active substance in disper- (a) a heterocycle of the formula sion or suspension. CH

The following examples further illustrate the produc- (A) H tion of some fungicidal agents: 2

EXAMPLE I (b f n (I) parts of 7-[13-(n-octylamino)-ethylamino]-3,4,5,6- l i gg i z g i igi Salt of the compound of tetrahydro-2H-azepine produced as described in Example R1 in Formula I representing hydrogen alkyl with 1 are finely m1lled n a ball mill with 4 parts of a polyfrom 1 to 15 carbon atoms, alk0X;,a1ky1 with vinyl pyrrolldone dispersing agent and 76 parts of water, from 3 to 15 carbon atoms alkylthioalkyl with The paste so obtained is suspended in water and is used from 3 to 15 Carbon atonls chloroalkyl with for the combatting of fungi, particularly in orchards. from 3 to 15 carbon atoms bromoalkyl with EXAMPLE II from 3 to 15 carbon atoms,

50 parts of 7-[ 3-(n-octylammo) -ethylam1n0]-3,4,5,6- p gfif xig F; -f g i;:; 315235 1 3 1 .311 tetrahydro-ZI-I-azeprne, produced as 1n Example 1, 2 parts alkyl, lower lk lhenyl-lower alkyl l wer of an adhesive having a polyvinyl alcohol base, 10 parts alkoxy phenyl lower alkyl chlorophe H3114 owe r of sulphite waste liquor, 16 parts of champagne chalk, alkyl bromophenyuower glkyl 20 parts of kaolin and 2 parts of a wettmg agent havlng cycloalkyl with from 5 to 7 Carbon atoms, lower an alkyl and aryl sulphonate base as milled together, alkylcycloalkyl with from 5 to 7 ring carbon mixed, and again milled. A 50% wettable powder is obatoms Al,s azacyclo pententyl (5) lower alkyl tained which can be suspended in water and is suitable in z e1openteny1-( 5) a -azaycloheptenylparticular for use in fruit cultivatlon. (7) lower alkyl 7zlzacycloheptenyl (7),

EXAMPLE III 40 A -azacyclononeny1-(9) or lower alkyl-A lononenyl(9 10 parts of 7-('y-phenylamino-propylamino)-3,4,5,6- azflcyc tetrahydrO-ZI-I-aZepine, produced as described in Example y i g q g g ffrom g n 4 are dissolved in 80 parts of dimethyl formamide, and i z gr; s i a Carson a of 10 parts of an alkyl-aryl sulphonate are mlxed into this g p g n zn being g membrs of g A solution until homogeneity is attained. In this way an emulsifiable solution is obtained which can be diluted to any concentration desired.

EXAMPLE IV 10 parts of 7-(v-phenylamino-propylamino)-3,4,5,6- tetrahydro-ZH-azepine, produced as described in Example 4, are dissolved in 15 parts of dimethyl sulphoxide and 65 parts of cyclohexanone. 10 parts of an alkylaryl polyethylene oxide (ratio 1:10) are mixed into this solution until homogeneity is attained. An emulsifiable solution is obtained which can be diluted to any concentration desired.

EXAMPLE V The fungicidal activity of the compounds of Formula I was determined by the germination test with spores of the following types of fungi: Allernaria tenuz's, Botrytis cinerea, Clasterosporium c., Coniothyrium dipL, Fusarium culm., Mucor spec., Penicillium spec., and Stemphyllium cons.

A determined amount of a 1%, 0.1% and 0.01% solution of active substances in acetone was placedall under equal conditions--in four petri dishes of identical size. The solvent was evaporated whereupon a level'coating of active substance ready for inoculation was obtained in each of the four dishes. After inoculation, the dishes were kept for 168 hours at 20 C. in an atmosphere of 80% humidity. The germinated spores were then counted. The following table shows the values at which at least a 90% inhibition of germination was attained. The value 2. A compound as defined in claim 1, wherein said heterocycle is 7 [B-(n-octylamino)-ethylamino] 3,4,5,-6- tetrahydro-ZH-azepine.

3. A compound as defined in claim 1, wherein said heterocycle is 7-( phenylamino propylamino) 3,4,5 ,6- tetrahydro-ZH-azepine.

4. A compound as defined in claim 1, wherein said heterocycle is 7-{B-[B'-(n-hexyloxy) ethylaminoJ-ethylamino}-3,4,5,6-tetrahydro-ZH-azepine.

5. A compound as defined in claim 1, wherein said heterocycle is 7-{ ti-[A azacycloheptenyl (7) amino]- ethyl-amino}-A -azacycloheptene.

6. A compound as defined in claim 1, wherein said heterocycle is 7-[5 (n pentadecylamino) ethylamino]- 3,4,5,6-tetrahydro-2H-azepine.

7. A compound as defined in claim 1, wherein said heterocycle is 9- ['y- (p-chlorobenzylamino -propylamino] A -azacyclononene.

8. A compound as defined in claim 1, wherein said heterocycle is 9-{,B [A azacyclononenyl-(9) amino]- ethylamino}-A -azacyclononene.

References Cited FOREIGN PATENTS 1,078,568 3/1960 Germany.

ALTON D. ROLLINS, Primary Examiner US. Cl. X.R. 

